University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia.
HIRO BIOTECH, Tokushima, Japan.
Environ Health Perspect. 2020 Oct;128(10):107005. doi: 10.1289/EHP6596. Epub 2020 Oct 16.
Endocrine-disrupting chemicals can interfere with hormonal homeostasis and have adverse effects for both humans and the environment. Their identification is increasingly difficult due to lack of adequate toxicological tests. This difficulty is particularly problematic for cosmetic ingredients, because testing is now banned completely in the European Union.
The aim was to identify candidate preservatives as endocrine disruptors by methods and to confirm endocrine receptors' activities through nuclear receptors .
We screened preservatives listed in Annex V in the European Union Regulation on cosmetic products to predict their binding to nuclear receptors using the Endocrine Disruptome and VirtualToxLab™ version 5.8 tools. Five candidate preservatives were further evaluated for androgen receptor (AR), estrogen receptor (), glucocorticoid receptor (GR), and thyroid receptor (TR) agonist and antagonist activities in cell-based luciferase reporter assays in AR-EcoScreen, , MDA-kb2, and GH3.TRE-Luc cell lines. Additionally, assays to test for false positives were used (nonspecific luciferase gene induction and luciferase inhibition).
Triclocarban had agonist activity on AR and at and antagonist activity on GR at and TR at . Triclosan showed antagonist effects on AR, , GR at and TR at , and bromochlorophene at (AR and TR) and at ( and GR). AR antagonist activity of chlorophene was observed [inhibitory concentration at 50% (IC) ], as for its substantial agonist at and TR antagonist activity at . Climbazole showed AR antagonist (), agonist at , and TR antagonist activity at .
These data support the concerns of regulatory authorities about the endocrine-disrupting potential of preservatives. These data also define the need to further determine their effects on the endocrine system and the need to reassess the risks they pose to human health and the environment. https://doi.org/10.1289/EHP6596.
内分泌干扰化学物质会干扰激素平衡，对人类和环境都有不良影响。由于缺乏充分的毒理学测试，它们的鉴定变得越来越困难。对于化妆品成分来说，这种困难尤其成问题，因为在欧盟，测试现已完全被禁止。
本研究旨在通过方法鉴定候选防腐剂是否为内分泌干扰物，并通过核受体确认内分泌受体的活性。
我们筛选了欧盟化妆品法规 Annex V 中列出的防腐剂，使用内分泌干扰组（Endocrine Disruptome）和 VirtualToxLab™ 版本 5.8 工具预测它们与核受体的结合。进一步在 AR-EcoScreen、、MDA-kb2 和 GH3.TRE-Luc 细胞系中，使用基于细胞的荧光素酶报告基因检测评估 5 种候选防腐剂的雄激素受体（AR）、雌激素受体（）、糖皮质激素受体（GR）和甲状腺受体（TR）激动剂和拮抗剂活性。此外，还使用了测试假阳性的检测（非特异性荧光素酶基因诱导和荧光素酶抑制）。
三氯卡班对 AR 和 具有激动剂活性，对 GR 具有拮抗剂活性（在 时），对 TR 具有拮抗剂活性（在 时）。三氯生对 AR、、GR（在 时）和 TR（在 时）具有拮抗剂作用，对溴氯酚（在 AR 和 TR 时）和（在 和 GR 时）具有拮抗剂作用。氯苯对 AR 的拮抗剂活性被观察到[半数抑制浓度（IC）为 ]，同时其对 的显著激动剂和对 TR 的拮抗剂活性分别为 。克霉唑对 AR 具有拮抗剂作用（），对 具有激动剂作用，对 TR 具有拮抗剂作用。
这些数据支持监管机构对防腐剂具有内分泌干扰潜力的担忧。这些数据还定义了需要进一步确定它们对内分泌系统的影响，以及需要重新评估它们对人类健康和环境构成的风险。https://doi.org/10.1289/EHP6596.
